Is ABCA3 p.Leu314= (c.942C>G) pathogenic?

ABCA3 p.Leu314= (c.942C>G) is classified Conflicting classifications of pathogenicity in ABCA3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-19). Rare (popmax 0.674%, mid); Associated with interstitial lung disease due to ABCA3 deficiency.

What condition is associated with ABCA3 p.Leu314= (c.942C>G)?

ABCA3 p.Leu314= (c.942C>G) is associated with interstitial lung disease due to ABCA3 deficiency, hereditary pulmonary alveolar proteinosis (ClinVar).

How common is ABCA3 p.Leu314= (c.942C>G) in the general population?

ABCA3 p.Leu314= (c.942C>G) is rare (popmax 0.674%, mid) (gnomAD).

ABCA3 p.Leu314=

Q: How is Interstitial lung disease due to ABCA3 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.942C>G · rs773723001 · VCV318563

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.674%, mid)

Conditions

interstitial lung disease due to ABCA3 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.28	GERP -4.7, phastCons 0.001
Overall
CADD	4.508	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.674% Middle Eastern · 41/6,084 alleles

Filtering AF 0.511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.453%

Overall 0.0105% 170/1,614,142 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.674%	148
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,701
Remaining individualsnot grpmax-eligible	0.016%	6,249
European (non-Finnish)	0.00864%	11,569
African / African-American	0.00534%	18,736
Admixed American	0.005%	20,004
South Asian	0.0022%	45,546

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCA3
Protein: p.Leu314=
Coding: c.942C>G
MANE Select: NM_001089
dbSNP: rs773723001
Type: single nucleotide variant
Location: chr16:2317696 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB
Residue 314: an α-helix

Full ABCA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

interstitial lung disease due to ABCA3 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary pulmonary alveolar proteinosis

For Interstitial lung disease due to ABCA3 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ABCA3 c.1112-20G>A Likely pathogenic ★★ same condition
ABCA3 c.2053-1G>C Likely pathogenic ★★ same condition
ABCA3 c.2414+1G>A Likely pathogenic ★★ same condition
ABCA3 c.3863-98C>T Pathogenic ★★ same condition
ABCA3 c.614-2A>G Likely pathogenic ★★ same condition
ABCA3 p.Ala1070Thr Likely pathogenic ★★ ⚠ same condition
ABCA3 p.Arg1550Trp Likely pathogenic ★★ same condition
ABCA3 p.Arg155Trp Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abca3-p-leu314 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown